大肠肿瘤结肠腺瘤病基因突变的特征

目的 研究早期大肠肿瘤结肠腺瘤病（adenomatous polyposis coli,APC)基因突变特征及可能的内在机理。方法 体外蛋白合成试验和序列分析确定115例非家族性腺瘤性息肉病大肠肿瘤的APC突变。结果 76例APC基因突变病例（101个突变点）中，移码突变为多（56％），91％为1－2bp碱基改变，其中2／3为碱基A，51％点突变在CpG岛。对比遗传性非息肉病性结直肠癌（hereditary nonpolyposis colorectal cancer,HNPCC)和散发性肿瘤的APC基因突变，HNPCC的移码突变明显多（69％对52％，P＜0．05），点突变在CpG位点分布明显少（31％对50％，P＜0．05）；另突变频率略低（53％对67％，P＞0．05），在片段3分布也略少（38％对46％，P＞0．05）。15例（20％）病例还检出双突变，间距介于7－1443bp。结论一些APC基因突变特征与DNA错配修复缺陷有关；HNPCC和散发性大肠肿瘤的APC基因突变存在差异；双突变位点间距相差甚远，提示等位与非等位基因突变并存。

Characteristics of APC gene mutations in colorectal tumors

Objective To investigate the mutational features of ade no matous polyposis coli (APC) gene and their possible arising mechanism in colorec tal tumors.Methods PCR-based IVSP assay (in vitro synthesized protein test) and sequence a na lysis were used to determine somatic mutations of whole APC gene in 115 cases wi th non familial adenomatous polyposis(non-FAP) colorectal tumors.Results Seventy-six mutated cases with 101 mutations were confirmed in the st u dy. Analysis of the spectra of APC mutations revealed that frameshift mutations w ere more common than point ones(56% vs 44%), ninety-one percent of them being i nsertions/deletions of 1-2 bp, particularly single A (61%) and 51% of point mut atio ns locating at CpG sites. In comparison with sporadic tumors, hereditary nonpoly posis colorectal cancer (HNPCC) was found to have more frameshift mutations ( 69% vs 52%, P<0.05) , less point mutations at CpG site(31% vs 50%, P<0 0 5) , and a slightly lower frequency of mutations(53% vs 67%, P>0 05) . The r e was no difference in mutational distribution of segment 3 between them (38% vs 46%, P>0 05) . It was also found that 15 cases(20%) had double mutations w ith distance ranging from 7 to 1443 bp, suggesting the coexistance of allelic an d non-allelic mutations.Conclusion Based on the mutational spect ra of APC gene in colorectal tumors, it can be concluded that most of gene mutat ions are probably related to DNA mismatch repair deficiency, and the APC mutatio nal patterns of HNPCC and sporadic tumors are quite different. The reason of coe xistance of allelic and non-allelic mutations needs to be investigated.